SPECT IMAGING OF ISCHEMIC MYOCARDIUM USING A TECHNETIUM-99M-NITROIMIDAZOLE LIGAND

This investigation evaluates the efficacy of a Tc-99m-labeled nitroimi dazole (BMS-181321) in identifying oxygen-deprived tissue in two canin e models of myocardial ischemia. Methods: For both models (A and B), e picardial microvascular oxygen pressure (mPO(2)) was monitored by meas uring the oxygen-dependent quenching of phosphorescence lifetime of Pa lladium mesotetra (4-carboxyphenyl) porphine. In Model A (beagles, n = 5), BMS-181321 was administered intravenously and a distal branch of the left anterior descending coronary artery (LAD) was ligated complet ely 40 sec later. Ten minutes later, the ligature was released establi shing tissue reoxygenation. In Model B, flow through the LAD was reduc ed until the mPO(2) was about 2 Torr. After bolus administration of BM S-181321 (50-60 mCi), coronary ischemia was continued for a residence period of up to 4 hr. Results: With Model A, SPECT reconstructions rev ealed a small ischemic area in three of five dogs, however, a transmur al accumulation of the compound was evident in the autoradiograms from all dogs. In the two animals in which the defect was not observed by SPECT, the ischemic episode had nominal effects on the ratio of +/-dp/ dt (<4% change as compared to baseline values). In Model B, SPECT reco nstructions showed positive images of the oxygen-deprived area within the mid- to apical regions of the left ventricle (n = 5). Autoradiogra phic analysis showed a transmural association with cells resulting in an ischemic-to-nonischemic ratio of 3.5 +/- 0.4 (n = 4) for animals wi th similar residence times. Conclusion: The results from both models s uggest that BMS-181321 provides a noninvasive marker of regional ische mia in the heart and that this compound may have clinical utility for detection of coronary artery disease.